A complex multi-molecular-weight hyaluronic acid three-dimensional moisturizing skin care composition
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- GUANGDONG KASEN IND CORP LTD
- Filing Date
- 2026-01-12
- Publication Date
- 2026-05-26
Smart Images
Figure CN122075338A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of daily chemical and cosmetic technology, specifically to a compound multi-molecular-weight hyaluronic acid three-dimensional moisturizing skin care composition. Background Technology
[0002] Currently, products used for lubrication and moisturizing of the skin or specific areas (such as the genital mucosa) are mainly divided into two categories: silicone oil-based and water-based. While silicone oil provides good lubrication, it tends to remain on the skin surface after use, making it difficult to rinse thoroughly with water. Furthermore, it may disrupt the natural balance of the skin's or mucous membrane microenvironment, posing certain safety risks. Therefore, developing safe and gentle, fully water-soluble moisturizing and lubricating systems has become a trend.
[0003] However, while hyaluronic acid (or sodium hyaluronate) and allantoin are common moisturizing and repairing ingredients in existing aqueous systems, their combined application still has significant drawbacks. Allantoin, as an amphoteric compound, can promote cell growth and soften keratin, exhibiting excellent soothing and repairing effects. However, its solubility in aqueous systems is low, and it is quite sensitive to temperature changes. When the amount of allantoin added to the formula is high (such as when used to enhance repair effects) or the ambient temperature decreases, the dissolved allantoin is prone to recrystallization and precipitation from the system. This precipitation not only causes the product's appearance to change from transparent to cloudy, disrupting the system's homogeneity, but the precipitated microcrystals can also create a noticeable grainy feel during application and rubbing, and may even scratch delicate skin or mucous membranes.
[0004] Furthermore, sodium hyaluronate (the common salt form of hyaluronic acid), a core moisturizing ingredient, is a linear polysaccharide, and its moisturizing efficacy is closely related to its molecular weight. In existing technologies, some products use only sodium hyaluronate with a single molecular weight, making it difficult to simultaneously address the needs of deep penetration and surface protection. While large-molecule sodium hyaluronate can form a hydration film on the skin surface to prevent moisture evaporation, it has difficulty penetrating the stratum corneum, and at high concentrations, it feels sticky. Under repeated friction, it is prone to pilling due to the fragility of the film. Small-molecule sodium hyaluronate, although having better permeability, has poor film-forming properties and cannot provide a long-lasting physical barrier, allowing moisture to easily escape.
[0005] Therefore, this invention proposes a compound multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition to overcome the shortcomings of the prior art. Summary of the Invention
[0006] To address the shortcomings of existing technologies, this invention provides a compound multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition, which solves the problems of high-concentration allantoin easily recrystallizing and precipitating in aqueous skin care systems, and the inability of single-molecular weight sodium hyaluronate to achieve both deep moisturizing and surface film formation, resulting in a sticky skin feel.
[0007] To address the above problems, the present invention provides the following technical solution: In a first aspect, the present invention provides a complex multi-molecular-weight hyaluronic acid three-dimensional moisturizing skin care composition, employing the following technical solution: A complex multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition, comprising the following components in weight percentage: 0.30%–0.60% high molecular weight sodium hyaluronate; 0.30%–0.70% medium molecular weight sodium hyaluronate; 0.05%–0.30% low molecular weight sodium hyaluronate; 0.30%–0.60% allantoin; 3.00%–6.00% trehalose; 0.30%–0.70% L-arginine; 0.40%–1.20% D-panthenol; 0.50%–1.20% preservative; appropriate amount of pH adjuster; and balance deionized water; wherein the pH value of the composition is 4.5–6.5, and the mass ratio of trehalose to allantoin is greater than or equal to 10:1.
[0008] By adopting the above technical solution, the present invention utilizes the synergistic effect of multiple components to construct a stable moisturizing system, the specific mechanism of action of which is as follows: First, L-arginine, as a basic amino acid, provides an alkaline environment in aqueous solution. L-arginine interacts with allantoin molecules, increasing the solubility of allantoin in the aqueous phase and preventing its direct precipitation at room temperature.
[0009] Secondly, trehalose molecules contain multiple hydroxyl groups, which can form hydrogen bonds with water molecules and allantoin molecules. When the mass ratio of trehalose to allantoin is controlled at 10:1 or higher, trehalose molecules form a hydration layer around allantoin molecules, producing a steric hindrance effect that hinders the aggregation of allantoin molecules, thereby inhibiting the formation of allantoin crystal nuclei.
[0010] Furthermore, sodium hyaluronates of different molecular weights are combined to form a cross-linked and entangled network structure. High-molecular-weight sodium hyaluronate provides a high-viscosity continuous phase, increasing resistance to solute diffusion, restricting the movement of allantoin molecules, and slowing the growth of microcrystal nuclei; medium- and low-molecular-weight sodium hyaluronates fill the gaps in the network structure, increasing the stability of the system.
[0011] Finally, D-panthenol, as a small-molecule moisturizer, can penetrate between the large molecular chains of sodium hyaluronate, improving the fluidity of the polymer. Simultaneously, D-panthenol further stabilizes the complex formed by trehalose and allantoin through hydrogen bonding.
[0012] In summary, this composition achieves stable high concentrations of allantoin under pH conditions of 4.5–6.5, exhibiting a uniform and transparent appearance.
[0013] Preferably, the weight percentages of the components are: 0.35%–0.50% high molecular weight sodium hyaluronate; 0.40%–0.60% medium molecular weight sodium hyaluronate; 0.10%–0.20% low molecular weight sodium hyaluronate; 0.35%–0.45% allantoin; 3.50%–5.25% trehalose; 0.40%–0.60% L-arginine; 0.50%–1.00% D-panthenol; and 0.60%–1.00% preservatives.
[0014] By adopting the above technical solution, the proportions of each component are within an optimal range. Within this range, trehalose can effectively inhibit allantoin crystallization and avoid the sticky feel caused by excessive trehalose; the amount of L-arginine can maintain the alkaline environment required for solubilization, and after adjusting the pH to slightly acidic, the viscosity of sodium hyaluronate will not be affected by excessive salt concentration.
[0015] Preferably, the specifications of the sodium hyaluronate are as follows: the weight-average molecular weight of the macromolecular sodium hyaluronate is 1.8 MDa to 2.2 MDa; the weight-average molecular weight of the medium-molecular-weight sodium hyaluronate is 0.8 MDa to 1.0 MDa; and the weight-average molecular weight of the small-molecular-weight sodium hyaluronate is less than 10 kDa.
[0016] By employing the above technical solution, three different molecular weights of sodium hyaluronate each play a specific role: the large molecules (1.8 MDa to 2.2 MDa) form a hydration film on the skin surface, reducing moisture loss; the medium molecules (0.8 MDa to 1.0 MDa) moisturize the stratum corneum; and the small molecules (less than 10 kDa) can penetrate the epidermis and bind moisture. This combination improves the film-forming properties and moisturizing longevity issues of single-molecular-weight products.
[0017] Preferably, the preservative is a solution of 1,2-hexanediol and p-hydroxyacetophenone in a mass ratio of 10:1; the pH adjuster is an aqueous solution of citric acid.
[0018] By employing the above technical solution, 1,2-hexanediol possesses preservative and moisturizing properties; p-hydroxyacetophenone exhibits antioxidant activity. The combination of these two components demonstrates good compatibility with the sodium hyaluronate system. Citric acid is used to adjust the pH to a slightly acidic level, and the citrate ion has an auxiliary chelating effect, helping to maintain the clarity of the system.
[0019] Preferably, the dry film formed after drying the composition has a transmittance greater than 95% at a wavelength of 550 nm, and at 25°C and a shear rate of 0.01 s⁻¹. -1 The zero-shear viscosity is greater than 40,000 mPa·s.
[0020] By adopting the above technical solution, the high light transmittance indicates that there is no obvious microcrystal precipitation inside the system and the components are uniformly dispersed; the high zero-shear viscosity indicates that a three-dimensional network structure has been established inside the system, which has good suspension stability.
[0021] Secondly, the present invention provides a method for preparing a compound multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition, which adopts the following technical solution: A method for preparing a compound multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition includes the following steps: S1. Preparation of solubilizing solution: Dissolve trehalose and L-arginine in water to form an alkaline environment, then add allantoin and D-panthenol, and stir until the solution is clear; S2, frequency conversion swelling: Add a mixture of high molecular weight sodium hyaluronate, medium molecular weight sodium hyaluronate and low molecular weight sodium hyaluronate powders under stirring, control the temperature to swell and form a homogeneous colloid; S3. Homogeneous neutralization: Slowly add an acidic solution to the system to adjust the pH until the pH value reaches 4.5-6.5, forming a transparent gel-like liquid; S4. Post-treatment: Add preservatives, degas and filter.
[0022] By adopting the above technical solution, this invention solves the problems of high-concentration active ingredient precipitation and difficult dispersion of polymers by first dissolving the insoluble components under alkaline conditions, then adding a polymer for thickening, and finally adjusting the pH value to a weakly acidic state. The specific process principle is as follows: In step S1, the alkalinity of L-arginine in aqueous solution is used to increase the solubility of allantoin, allowing it to dissolve in the aqueous phase. The pre-dissolution of trehalose utilizes its hydration capacity to stabilize allantoin molecules and prevents competitive adsorption of subsequently added D-panthenol, ensuring a clear bottom solution.
[0023] In step S2, sodium hyaluronate powder is added to the alkaline solution. Since the solute is already present in the solution, the water activity decreases, slowing down the wetting rate of the powder surface and preventing the powder particles from rapidly absorbing water and gelling, thus hindering internal dissolution. The sodium hyaluronate molecular chains unfold under stirring, increasing the system viscosity and constructing a three-dimensional network, dispersing the dissolved allantoin molecules within the network.
[0024] In step S3, once the system reaches a high viscosity, an acidic solution is added to adjust the pH value. Although the decrease in pH leads to a reduction in the theoretical solubility of allantoin, the diffusion of allantoin molecules is restricted due to the barrier effect of the high-viscosity polymer network and the steric hindrance effect of trehalose, making it difficult for them to aggregate and form crystal nuclei. This process sequence achieves a transition from an alkaline dissolved state to a high-viscosity suspended state, ensuring the stability of allantoin in the final weakly acidic product.
[0025] Preferably, in step S1, the system temperature is controlled at 25℃~30℃; the pH value of the solution after adding trehalose and L-arginine is about 10.0; and the stirring time after adding allantoin and D-panthenol is 15~20 minutes.
[0026] By employing the above technical solution, temperature control of 25℃~30℃ avoids excessively slow degradation or dissolution rates of the raw materials. A pH of approximately 10.0 is a result of the natural dissociation of L-arginine, an environment sufficient to promote allantoin dissolution. A stirring time of 15~20 minutes ensures complete dissolution of all solid raw materials.
[0027] Preferably, the variable frequency swelling in step S2 is specifically as follows: first, the stirring speed is increased to 800 rpm to 1000 rpm to form a vortex, and the mixed powder is sprinkled into the center of the vortex; after the powder is dispersed, the stirring speed is immediately reduced to 200 rpm to 300 rpm, and the system temperature is maintained below 30°C, and the stirring is continued at low speed for 45 to 60 minutes.
[0028] By adopting the above technical solution, the problems of dispersion and viscosity maintenance are solved by combining high and low speeds. First, the shear force and eddy current generated by the high speed rapidly disperse the sodium hyaluronate powder, preventing particle adhesion. Second, immediately after dispersion, the stirring speed is switched to low to avoid prolonged high-speed shearing that could break the molecular chains and reduce the viscosity of the finished product. The combination of low-speed stirring and low-temperature control provides a suitable environment for the swelling of the molecular chains.
[0029] Preferably, in step S3, the acidic solution is a citric acid aqueous solution with a mass fraction of 10% to 15%; it is added by a fine drip or multi-point spray, and the dripping position is close to the edge of the stirring blade.
[0030] The above technical solution is employed to prevent crystallization caused by localized over-acidity. If the acid is added unevenly, the local pH at the contact point will drop rapidly, leading to the precipitation of allantoin in that area. Using a fine drip or multi-point spray, and adding the acid near the edge of the stirring blades, allows the acid to be rapidly dispersed throughout the system, ensuring a uniform decrease in overall pH and maintaining system transparency.
[0031] Preferably, in step S4, the preservative is a solution of 1,2-hexanediol and p-hydroxyacetophenone mixed in a mass ratio of 10:1; the degassing treatment is carried out under a vacuum of -0.08 MPa to -0.09 MPa; and the filtration is performed using a 200-mesh filter.
[0032] By employing the above technical solutions, the premixing and dissolving of preservatives avoids excessively high local concentrations or uneven dissolution. Vacuum degassing removes air bubbles from the system, improving the product's appearance quality. The filtration step traps any impurities or incompletely swollen polymer particles.
[0033] This invention provides a complex multi-molecular-weight hyaluronic acid three-dimensional moisturizing skincare composition. It possesses the following beneficial effects: 1. This invention solves the technical problem of high-concentration allantoin's poor solubility and easy precipitation in aqueous skin care systems through component compounding. The system utilizes the alkaline environment provided by L-arginine to improve the initial solubility of allantoin, and uses a high proportion of trehalose to form a hydration layer around the allantoin molecules, generating a steric hindrance effect to prevent molecular aggregation. Combined with the limiting effect of sodium hyaluronate network on solute diffusion, the composition can maintain physical stability even after being finally adjusted to a weakly acidic pH value. The finished product is clear and transparent, without the precipitation of crystal particles, avoiding physical irritation to the skin or mucous membranes caused by microcrystals.
[0034] 2. This invention uses a compound of three different molecular weights of sodium hyaluronate—large, medium, and small—to construct a three-dimensional, layered moisturizing system. Large molecular weight sodium hyaluronate forms a hydration film on the skin surface to reduce moisture evaporation, while medium and small molecular weight sodium hyaluronate penetrate the stratum corneum and epidermis to bind moisture. Simultaneously, D-panthenol, acting as a plasticizer, inserts between the polymer chains, increasing their flexibility. Combined with the "amorphous vitreous" structure constructed by trehalose, this not only improves the problem of strong film-forming properties and pilling associated with single-molecule hyaluronic acid but also gives the product excellent immediate lubrication and anti-friction properties. This formula eliminates traditional silicone oil components, is a fully water-soluble system, is easy to rinse without residue, and is more conducive to maintaining the health of the microenvironment of intimate areas and sensitive regions.
[0035] 3. The preparation method provided by this invention employs variable frequency swelling and a specific feeding sequence to ensure the high viscosity and uniformity of the product. Dissolving small molecule solutes first reduces the activity of water, slowing down the swelling rate of the sodium hyaluronate powder surface and preventing powder agglomeration. Combining high-speed dispersion with low-speed swelling achieves rapid and uniform powder dispersion while avoiding polymer chain breakage and viscosity loss caused by prolonged high shear forces, maximizing the retention of the polymer's thickening effect. This results in a product that combines gel stability during resting with a silky smooth feel during use. Attached Figure Description
[0036] Figure 1 This is a comparison chart of the dry film light transmission performance of Examples 1-5 in Test Example 2 of the present invention; Figure 2 The diagram shows the rheological properties and resistance to nucleation-induced stability of each group of samples in Test Example 3 of the present invention; wherein, (a) shows the zero-shear viscosity of Example 1 and each comparative example; and (b) shows the turbidity increase after 72 hours of exogenous seed induction. Figure 3 This is a comparison chart of the shedding rates of dry films in each group of samples under shear stress in Test Example 4 of the present invention. Detailed Implementation
[0037] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0038] The main raw materials and reagents used in the following examples and comparative examples have the following sources and specifications. Reagents not specifically mentioned are all commercially available analytical grade or higher grade products.
[0039] Sodium hyaluronate, CAS No. 9067-32-7, is specifically divided into three specifications in this invention: high molecular weight sodium hyaluronate with a weight average molecular weight of 1.8 MDa-2.2 MDa; medium molecular weight sodium hyaluronate with a weight average molecular weight of 0.8 MDa-1.0 MDa; and low molecular weight sodium hyaluronate with a weight average molecular weight of less than 10 kDa.
[0040] Allantoin, CAS No. 97-59-6, content greater than 98.0%.
[0041] Trehalose, CAS No. 6138-23-4, is a dihydrate with a purity greater than 98.0%.
[0042] L-arginine, CAS number 74-79-3, is an L-type free base with a purity greater than 98.5%.
[0043] D-Panthenol, CAS No. 81-13-0, purity greater than 98.0%.
[0044] 1,2-Hexanediol (CAS No. 6920-22-5), p-hydroxyacetophenone (CAS No. 99-93-4), and citric acid (CAS No. 5949-29-1) are all commercially available analytical grade raw materials. The "mixture of 1,2-hexanediol and p-hydroxyacetophenone" refers to a solution prepared by mixing the two in a mass ratio of 10:1.
[0045] Deionized water, CAS No. 7732-18-5, conductivity less than 10 μS / cm.
[0046] Preparation Example 1: This preparation example provides a general method for preparing a compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition, including the following steps: (1) Preparation of the solubilizing solution: In a reactor equipped with a jacketed cooling device and a variable frequency stirring paddle, add 80% of the total amount of deionized water according to the formula, turn on the cooling circulating water to control the temperature inside the reactor to be constant at 25℃; turn on the stirring and set the speed to 400 rpm; add the formula amount of trehalose and L-arginine in sequence, and continue stirring for 10 minutes until the solid is completely dissolved and the solution is colorless and transparent, and the pH value is measured to be about 10.0; then add the formula amount of allantoin and D-panthenol to the solution, and maintain the stirring speed at 400 rpm for 20 minutes until the solution is completely clear and there are no visible suspended particles.
[0047] (2) Variable frequency swelling: Increase the stirring speed to 1000 rpm to form a deep vortex on the liquid surface. Quickly and evenly sprinkle the mixed powder of large molecular weight sodium hyaluronate, medium molecular weight sodium hyaluronate and small molecular weight sodium hyaluronate into the center of the vortex within 3 minutes. After the powder is dispersed, immediately reduce the stirring speed to 200 rpm to make the liquid flow into a laminar flow state. Maintain the temperature inside the vessel below 28°C and continue stirring at low speed for 60 minutes until the system is completely swollen and presents a uniform, high viscosity and high transparency fluid state.
[0048] (3) Homogeneous neutralization: Dissolve citric acid crystals in deionized water to prepare a 10% citric acid solution; keep the stirring speed at 200 rpm and slowly add the citric acid solution into the vessel by dripping it in a thin stream. The dripping position is close to the edge of the stirring blade. Monitor the pH value in real time. Stop dripping when the pH reaches the set value of the formula (e.g., 5.8); continue stirring for 15 minutes and observe the material to confirm that it is a transparent gel-like liquid without precipitation or turbidity.
[0049] (4) Post-treatment: Add the amount of 1,2-hexanediol and p-hydroxyacetophenone mixture according to the formula, stir at low speed until uniform; degas at a vacuum of -0.09MPa until there are no bubbles in the material; finally filter through a 200-mesh filter to obtain the final product.
[0050] Preparation Example 2: This preparation example provides another general method for preparing a compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition, including the following steps: (1) Preparation of the solubilizing solution: Add 85% of the total amount of deionized water to the reactor and control the temperature inside the reactor to be constant at 30°C; turn on the stirrer and set the speed to 300 rpm; add trehalose and L-arginine in sequence and stir to dissolve; then add allantoin and D-panthenol and maintain the stirring speed at 300 rpm for 15 minutes until completely clear.
[0051] (2) Variable frequency swelling: Increase the stirring speed to 800 rpm, sprinkle the three kinds of sodium hyaluronate mixed powder into the mixture within 5 minutes, and immediately reduce the stirring speed to 300 rpm after dispersion, maintain the temperature inside the vessel below 30°C, and continue stirring at low speed for 45 minutes until the system is completely swollen and uniform.
[0052] (3) Homogeneous neutralization: Use a 15% dilute citric acid solution; keep the stirring speed at 150 rpm, add it to the vessel by multi-point spraying, adjust the pH value to the formula setting value (e.g., 6.0); continue stirring for 10 minutes to confirm steady state.
[0053] (4) Post-treatment: Add preservative mixture, degas under vacuum of -0.08MPa, filter through 200 mesh filter to obtain the final product.
[0054] Example 1: This example provides a compound multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition, the weight percentage of each component is as follows: 0.45% high molecular weight sodium hyaluronate; 0.50% medium molecular weight sodium hyaluronate; 0.15% low molecular weight sodium hyaluronate; 0.40% allantoin; 4.50% trehalose; 0.50% L-arginine; 0.80% D-panthenol; 0.80% mixture of 1,2-hexanediol and p-hydroxyacetophenone; appropriate amount of 10% citric acid aqueous solution (adjust pH to 5.8); balance deionized water.
[0055] The preparation method used is the general preparation method described in Preparation Example 1.
[0056] Example 2: This example provides a compound multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition, the weight percentage of each component is as follows: 0.35% high molecular weight sodium hyaluronate; 0.40% medium molecular weight sodium hyaluronate; 0.10% low molecular weight sodium hyaluronate; 0.35% allantoin; 3.50% trehalose; 0.40% L-arginine; 0.50% D-panthenol; 0.60% mixture of 1,2-hexanediol and p-hydroxyacetophenone; appropriate amount of 15% citric acid aqueous solution (adjust pH to 6.0); balance deionized water.
[0057] The preparation method used is the general preparation method described in Preparation Example 2.
[0058] Example 3: This example provides a compound multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition, the weight percentage of each component is as follows: 0.50% high molecular weight sodium hyaluronate; 0.60% medium molecular weight sodium hyaluronate; 0.20% low molecular weight sodium hyaluronate; 0.45% allantoin; 5.00% trehalose; 0.60% L-arginine; 1.00% D-panthenol; 1.00% mixture of 1,2-hexanediol and p-hydroxyacetophenone; appropriate amount of 10% citric acid aqueous solution (adjust pH to 5.5); balance deionized water.
[0059] The preparation method used is the general preparation method described in Preparation Example 1.
[0060] Example 4: This example provides a compound multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition, the weight percentage of each component is as follows: 0.40% high molecular weight sodium hyaluronate; 0.55% medium molecular weight sodium hyaluronate; 0.15% low molecular weight sodium hyaluronate; 0.35% allantoin; 5.25% trehalose; 0.45% L-arginine; 0.75% D-panthenol; 0.75% mixture of 1,2-hexanediol and p-hydroxyacetophenone; appropriate amount of 15% citric acid aqueous solution (adjust pH to 5.9); balance deionized water.
[0061] The preparation method used is the general preparation method described in Preparation Example 2.
[0062] Example 5: This example provides a compound multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition, the weight percentage of each component is as follows: 0.35% high molecular weight sodium hyaluronate; 0.60% medium molecular weight sodium hyaluronate; 0.20% low molecular weight sodium hyaluronate; 0.40% allantoin; 4.20% trehalose; 0.55% L-arginine; 0.90% D-panthenol; 0.90% mixture of 1,2-hexanediol and p-hydroxyacetophenone; appropriate amount of 10% citric acid aqueous solution (adjust pH to 5.8); balance deionized water.
[0063] The preparation method used is the general preparation method described in Preparation Example 1.
[0064] Comparative Example 1: Compared with Example 1, the difference is that trehalose is not added, the missing weight is made up by deionized water, and the other raw materials and preparation steps are the same.
[0065] Comparative Example 2: Compared with Example 1, the difference is that the amount of trehalose added is reduced to 2.00% (at this time, the mass ratio of trehalose to allantoin is 5:1, which is lower than the 10:1 required by the present invention). The reduced weight is made up by deionized water, and the other raw materials and preparation steps are the same.
[0066] Comparative Example 3: Compared with Example 1, the difference is that L-arginine is not added. In step (1), after trehalose is added and dissolved, 1 mol / L sodium hydroxide solution is added dropwise to adjust the pH of the system to 10.0. Then allantoin and D-panthenol are added. The other raw materials and preparation steps are the same.
[0067] Comparative Example 4: Compared with Example 1, the difference is that D-panthenol is not added, the missing weight is made up by deionized water, and the other raw materials and preparation steps are the same.
[0068] Comparative Example 5: Compared with Example 1, the difference is that step (2) in the preparation process is changed, and the frequency conversion swelling is changed to high shear dispersion throughout the process. That is, after adding sodium hyaluronate powder, the high speed of stirring at 1000 rpm is maintained for 60 minutes. The other raw material ratios and other steps are the same.
[0069] Comparative Example 6: Compared with Example 1, the difference is that step (3) in the preparation process is changed, and the homogeneous neutralization is changed to concentrated acid rapid neutralization, that is, a 50% citric acid solution is added to the kettle at one time for adjustment. The other raw material ratios and other steps are the same.
[0070] Test Example 1: Verification of the system's low-temperature kinetic stability and the amorphous properties of the dry film Experimental description: 200g of each of the composition samples prepared in Examples 1-5 were selected and dispensed into transparent and clean borosilicate glass bottles, filling the bottles to 80% of their volume, and then sealed.
[0071] Low-temperature static test: Each group of samples was placed in a constant temperature incubator set at 4℃±0.5℃ and stored statically for 30 days without shaking. On the 30th day, the samples were taken out and observed visually under a standard light source box to check for clarity, presence of flocculent matter, or crystal precipitation at the bottom.
[0072] Cyclic temperature stress test: Take another sample and place it in a high and low temperature test chamber. Cycle it according to the procedure of constant temperature at 40℃ for 12 hours, cooling down to 25℃ and holding for 4 hours, cooling down to -5℃ and holding for 12 hours. A total of 5 complete temperature cycle cycles are performed. After the cycle, take it out and return it to room temperature to observe the appearance of the sample.
[0073] Dry film transmittance test: Take about 0.5g of each group of samples and coat them onto the surface of a clean glass slide using a wet film preparation device, controlling the wet film thickness to be 100μm; place the coated glass slide in a constant temperature and humidity chamber at 25℃ and 50% relative humidity for 24 hours to form a solid dry film; use a UV-Vis spectrophotometer, with a blank glass slide as a reference, to measure the transmittance of the dry film at a wavelength of 550nm, and measure each group of samples in parallel 3 times and take the average value.
[0074] The experimental data are shown in Table 1: Table 1: Stability and dry film transmittance test results of Examples 1-5 Conclusion: According to the test data in Table 1, Examples 1 to 5 maintained a clear and transparent homogeneous state after undergoing harsh long-term storage at low temperature (4°C) and drastic temperature cycling from -5°C to 40°C, without any visible crystal precipitation or flocculation.
[0075] From a kinetic perspective, the allantoin concentration in Example 3 reached 0.45%, which theoretically far exceeds its saturation solubility at 4°C. However, experimental results showed no phase separation. This confirms the synergistic effect of the "trehalose cage effect" and the "high-viscosity polymer network" constructed in this invention, effectively confining allantoin molecules within the solvated shell and greatly increasing the activation energy for crystal nucleation. Even in the thermodynamically unstable supersaturated state, the molecular motion within the system is subject to both steric hindrance and electrostatic interactions, resulting in a long-lasting metastable state, thus verifying the effectiveness of the "kinetic locking" mechanism.
[0076] The dry film transmittance data further revealed the microstructure in the solid state. Crystalline materials, due to their anisotropy and the presence of grain boundaries, typically cause light scattering, thus reducing transmittance. Data showed that the dry film transmittance of all embodiments was higher than 95%, with Example 1 reaching 98.42%, approaching the transmittance level of optical glass. This physical data indicates that during the water evaporation process, trehalose and D-panthenol successfully suppressed the crystallization habit of allantoin, preventing the arrangement of a regular lattice. The dried film layer was not composed of microcrystalline aggregates, but rather formed an isotropic amorphous glass. The transmittance of Examples 2 and 3 was slightly lower than that of Example 1, presumably because when the component concentration approached the critical value (too low or too high), there might be nanoscale non-uniform distribution in the micro-regions, leading to a very small amount of Rayleigh scattering, but the overall structure still fully conformed to the characteristics of an amorphous solid. This result directly supports the technical concept of "vitrification toughening" in this invention, indicating that a dense hydrogen bond cross-linking network was formed between the components.
[0077] Test Example 2: Characterization of Dry Film Optical Properties and Glass Transition Level Experimental description: To further quantify the microscopic uniformity of the dry film and to statistically verify and double-validate the preliminary transmittance data in Test Example 1, this test example employed a more rigorous parallel sample collection and precise measurement procedure. Specifically: The composition samples prepared in Examples 1 to 5 were selected.
[0078] Prepare a standard optical slide with dimensions of 25.4mm × 76.2mm, ultrasonically clean it with anhydrous ethanol for 15 minutes, and then air dry it.
[0079] Using a precision wet film preparation device (coating device), each group of samples was picked up and coated onto the effective area in the center of the glass slide. The wet film thickness was controlled at 100 μm, and the coating speed was controlled at 10 cm / s to ensure that the film layer was flat and uniform.
[0080] The coated glass slide is placed in a constant temperature and humidity chamber, with the ambient temperature set at 25°C and the relative humidity (RH) at 50%, and allowed to dry naturally for 24 hours until the weight of the film no longer changes, forming a solid dry film.
[0081] Turn on the UV-Vis spectrophotometer and preheat for 30 minutes. Using an uncoated blank slide as a reference, place the prepared dry film sample in the optical path, set the scanning range to 400nm-800nm, and record the transmittance (T%) at 550nm wavelength.
[0082] Three parallel samples were prepared for each group of samples, and the tests were conducted and the data were recorded.
[0083] The experimental data are shown in Table 2: Table 2: Test Results of Light Transmission Performance of Dry Films in Examples 1-5 Conclusion: Based on Table 2 and the appendix Figure 1 According to the test data, the dry films formed in Examples 1 to 5 all exhibited extremely high optical transparency in the visible light region (550nm), with average transmittance ranging from 95.77% to 98.43%. Among them, the data of Example 1 showed the best performance, with its transmittance approaching the limit of optical glass substrates and a relative standard deviation (RSD) of only 0.11%, indicating that the film layer texture was highly uniform.
[0084] From the perspective of solid-state physics and crystal chemistry, the optical transparency of a substance is closely related to the orderliness of its internal microstructure. Allantoin, as a high-melting-point crystalline substance, readily precipitates micron-sized or even millimeter-sized needle-like crystals during conventional drying processes. These crystal interfaces cause refraction and diffuse reflection of light, resulting in a hazy or opaque film.
[0085] The test results confirm that significant phase transition behavior was controlled during the solvent (water) evaporation process. Trehalose molecules, due to their polyhydroxy structure, rapidly formed a strong hydrogen bond network with the polar groups between sodium hyaluronate and allantoin molecules through "water substitution" as water was gradually lost. This high-density hydrogen bond cross-linking network effectively froze the movement of the molecular chains, preventing the migration of allantoin molecules to lattice nodes and their ordered stacking.
[0086] Meanwhile, D-panthenol, acting as a small-molecule plasticizer, intercalates between polymer segments, further disrupting the potential crystallinity. The resulting dry film is not a traditional crystal-polymer blend, but rather a thermodynamically homogeneous "amorphous glass." This glassy structure is isotropic, lacking grain boundaries or phase separation regions sufficient to cause visible light scattering, thus exhibiting extremely high light transmittance on a macroscopic scale. This result strongly demonstrates that the present invention successfully achieves vitrification and toughening modification of sparingly soluble active materials through a multi-component system with specific proportions.
[0087] Test Example 3: Comprehensive Test of Rheological Properties and Resistance to Nucleation-Induced Stability Experimental description: Samples prepared in Examples 1, 3, 5 and 6 were placed in a constant temperature environment at 25°C for 24 hours to equilibrate and eliminate thermal history.
[0088] A rotational rheometer equipped with a 40mm cone plate clamp was used, with the temperature set at 25℃, to perform steady-state shear scanning. The shear rate range was set to 0.01-100s. -1 The shear rate is taken as 0.01 s. -1 The viscosity value at that time is recorded as the zero-shear viscosity.
[0089] The initial turbidity values of each group of samples were determined using a high-precision benchtop turbidimeter.
[0090] Allantoin ultrafine powder (particle size <10μm) with a mass fraction of 0.05% was precisely added to each group of samples as exogenous seed crystals, and the samples were dispersed evenly by vortex mixing at low speed for 30 seconds.
[0091] The inoculated samples were placed in a 4°C constant temperature shaking incubator and the rotation speed was set to 100 rpm for continuous dynamic culture for 72 hours to simulate the nucleus-induced growth process under extreme conditions.
[0092] After the culture was completed, the final turbidity value of each group of samples was measured again, and the turbidity increment was calculated: Turbidity increment = final turbidity value - initial turbidity.
[0093] The experimental data are shown in Table 3: Table 3: Statistical analysis of zero-shear viscosity and turbidity changes after seeding induction for each group of samples Conclusion: Based on Table 3 and the appendix Figure 2 The test data showed that different formulation components and process parameters affected the rheological properties and anti-crystallization stability of the system.
[0094] Example 1 exhibited the highest zero-shear viscosity (48,250 mPa·s) and the lowest turbidity increment (2.33 NTU). This indicates that the "variable frequency flexible swelling" process effectively preserved the long-chain structure of the large-molecule sodium hyaluronate without significant shear degradation. This high-viscosity matrix constitutes a dense spatial network, and when exogenous seed crystals are introduced, the physical steric hindrance of the polymer chain segments greatly restricts the diffusion rate of allantoin molecules, preventing them from migrating to the seed crystal surface for lattice stacking, thus achieving "kinetic locking".
[0095] In contrast, Comparative Example 5, employing a high-shear process throughout, exhibited a significant decrease in zero-shear viscosity to 14,890 mPa·s, approximately 30% of that in Example 1. This viscosity loss directly weakened the physical barrier, resulting in a surge in turbidity increment to 83.72 NTU under seed-induced conditions. This data underscores the necessity of strictly controlling the shear rate in this invention to maintain the system's "kinetic stability."
[0096] Comparative Example 3, due to the lack of L-arginine, not only had difficulty establishing the initial state of dissolution, but also failed to form a fully extended gel network due to the lack of electrostatic interaction between the guanidine group and the sodium hyaluronate carboxyl group. The viscosity was low and it could not suppress the precipitation of allantoin, with a turbidity increase of up to 155.57 NTU.
[0097] The data from Comparative Example 6 reveal the criticality of the "dilute acid slow dripping" process. Although its final viscosity (45,610 mPa·s) was close to that of Example 1, the rapid neutralization with concentrated acid caused a sudden spike in local supersaturation, resulting in an initial turbidity (12.45 NTU) significantly higher than that of Example 1. These pre-existing microcrystal nuclei acted as catalysts for explosive crystallization in subsequent seed-induction experiments, leading to a maximum turbidity increase (232.65 NTU). This demonstrates that once the thermodynamic initial state is disrupted, simply increasing viscosity is insufficient to restore the system's stability, confirming the decisive role of process details in constructing a high-energy-barrier metastable system.
[0098] Test Example 4: Quantitative Test of Dry Film Toughness and Resistance to Friction (Anti-pilling) Experimental description: Standard-sized (38mm in diameter) biomimetic textured polyurethane (PU) synthetic leather was cut as a simulated skin base. The surface was gently wiped with anhydrous ethanol to remove grease and dust. After equilibration in a desiccator for 24 hours, the initial mass of each base was accurately weighed using a 1 / 100,000 electronic balance and denoted as W0.
[0099] Take 0.50g (accurate to 0.001g) of each of the samples from Example 1, Comparative Example 1, Comparative Example 2 and Comparative Example 4, and apply them evenly to the textured surface of the PU leather using an adjustable coating stick to ensure consistent coverage. Then place the samples in a 37°C constant temperature drying oven to dry for 4 hours until constant weight is achieved.
[0100] Remove the dried PU leather with the film layer, cool it to room temperature, and weigh it again accurately, recording the weight as W1. At this point (W1) W0) is the initial mass of the solid dry film.
[0101] The prepared sample was fixed on the sample stage of the Martindale abrasion tester, and standard wool felt was selected as the friction medium. The friction pressure was set to 2 kPa (simulating the pressure of lightly pressing and applying with the fingertip), the running mode was Lissajous graphic trajectory, and the number of reciprocating friction cycles was set to 50.
[0102] After the friction process is completed, remove the sample and use a bulb syringe and a soft brush to gently remove the debris and particles that have been detached from the surface due to friction. After confirming that there are no loose residues, weigh it accurately for the third time and record it as W2.
[0103] According to the formula D=[(W1 W2) / (W1 The film shedding rate (D) was calculated by multiplying W0) by 100%. Each group of samples was tested in parallel for 3 times, and the average value was taken.
[0104] The experimental data are shown in Table 4: Table 4: Statistics on the shearing rate (simulated rubbing amount) of dry film in each group of samples under shear stress Conclusion: Based on Table 4 and the appendix Figure 3 The test data showed that solid dry films constructed with different formulation systems exhibited drastically different mechanical properties when subjected to tangential shear stress (simulating a rubbing action).
[0105] The film peeling rate in Example 1 was only 2.72%, and macroscopically, the film surface remained smooth and intact, with no obvious peeling. This result confirms that the present invention successfully constructed a highly tough amorphous glass structure through a high-proportion compound of trehalose and D-panthenol. When subjected to an external shear force of 2 kPa, the molecular chain segments inside the glass film can undergo limited viscous flow to dissipate energy, rather than experiencing brittle fracture due to stress concentration. Trehalose replaces water molecules in the polymer chain spaces through a hydrogen bond network, maintaining the intermolecular distance and preventing excessively dense stacking of sodium hyaluronate segments.
[0106] Comparative Example 1, in the absence of trehalose, showed a peeling rate as high as 68.85%, indicating significant structural damage and exfoliation of the film. This is because sodium hyaluronate and allantoin alone tend to form rigid and brittle crystalline or glassy phases during the drying process. Under shear force, the film lacking toughening agent cannot undergo plastic deformation. When the stress exceeds the material's yield limit, it directly leads to the instantaneous propagation of microcracks, manifested as a large amount of debris detachment.
[0107] The data from Comparative Example 2 (dropout rate 25.30%) and Comparative Example 4 (dropout rate 16.79%) further quantified the synergistic effect of each component. Comparative Example 2 confirmed that if the mass ratio of trehalose to allantoin is less than 10:1, it is insufficient to form a complete solvation embedding, and the partially exposed crystalline regions become structural weaknesses. Comparative Example 4 showed that although trehalose provides a basic anti-crystallization effect, the lack of D-panthenol, a small-molecule intramolecular plasticizer, results in insufficient free volume of the film layer and a significant decrease in its flexibility. In summary, the ultra-low dropout rate of Example 1 is a comprehensive effect of "anti-crystallization-plasticization-vitrification" modification achieved synergistically by multiple components in a specific ratio.
[0108] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.
Claims
1. A complex multi-molecular-weight hyaluronic acid three-dimensional moisturizing skincare composition, characterized in that, The composition comprises the following components by weight percentage: High molecular weight sodium hyaluronate 0.30%–0.60%; Medium molecular weight sodium hyaluronate 0.30%–0.70%; Small molecule sodium hyaluronate 0.05%~0.30%; Allantoin 0.30%–0.60%; Trehalose 3.00%–6.00%; L-arginine 0.30%–0.70%; D-Panthenol 0.40%~1.20%; Preservatives: 0.50%–1.20%; pH adjuster in appropriate amount; Deionized water balance; The composition has a pH value of 4.5 to 6.5, and the mass ratio of trehalose to allantoin is greater than or equal to 10:
1.
2. The compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition according to claim 1, characterized in that, The weight percentage of the components is: High molecular weight sodium hyaluronate 0.35%–0.50%; Medium molecular weight sodium hyaluronate 0.40%–0.60%; Small molecule sodium hyaluronate 0.10%~0.20%; Allantoin 0.35%–0.45%; Trehalose 3.50%–5.25%; L-arginine 0.40%–0.60%; D-Panthenol 0.50%~1.00%; Preservatives: 0.60%–1.00%.
3. The compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition according to claim 1, characterized in that, The specifications of the sodium hyaluronate are as follows: The weight-average molecular weight of the high molecular weight sodium hyaluronate is 1.8 MDa to 2.2 MDa; The medium molecular weight sodium hyaluronate has a weight-average molecular weight of 0.8 MDa to 1.0 MDa. The weight-average molecular weight of the sodium hyaluronate is less than 10 kDa.
4. The compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition according to claim 1, characterized in that, The preservative is a solution of 1,2-hexanediol and p-hydroxyacetophenone in a mass ratio of 10:1; the pH adjuster is an aqueous solution of citric acid.
5. The compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition according to claim 1, characterized in that, The dry film formed after drying the composition has a transmittance of greater than 95% at a wavelength of 550 nm, and at 25°C and a shear rate of 0.01 s⁻¹. -1 The zero-shear viscosity is greater than 40,000 mPa·s.
6. A method for preparing a compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition according to any one of claims 1-5, characterized in that, Includes the following steps: S1. Dissolve trehalose and L-arginine in water to form an alkaline environment, then add allantoin and D-panthenol, and stir until the solution is clear; S2. Add a mixture of large-molecule sodium hyaluronate, medium-molecule sodium hyaluronate and small-molecule sodium hyaluronate powders while stirring, and control the temperature to allow swelling and form a homogeneous colloid. S3. Slowly add an acidic solution to the system to adjust the pH until the pH value reaches 4.5-6.5, forming a transparent gel-like liquid; S4. Add preservatives, degas and filter.
7. The method for preparing the compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition according to claim 6, characterized in that, In step S1, the system temperature is controlled at 25℃~30℃; the pH of the solution after adding trehalose and L-arginine is about 10.0; and the stirring time after adding allantoin and D-panthenol is 15~20 minutes.
8. The method for preparing the compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition according to claim 6, characterized in that, Step S2 is as follows: First, increase the stirring speed to 800 rpm to 1000 rpm to form a vortex, and sprinkle the mixed powder into the center of the vortex; after the powder is dispersed, immediately reduce the stirring speed to 200 rpm to 300 rpm, and maintain the system temperature below 30°C, and continue stirring at low speed for 45 to 60 minutes.
9. The method for preparing the compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition according to claim 6, characterized in that, In step S3, the acidic solution is a citric acid aqueous solution with a mass fraction of 10% to 15%; it is added by dripping or spraying at multiple points, and the dripping position is close to the edge of the stirring blade.
10. The method for preparing the compounded multi-molecular weight hyaluronic acid three-dimensional moisturizing skin care composition according to claim 6, characterized in that, In step S4, the preservative is a solution of 1,2-hexanediol and p-hydroxyacetophenone mixed in a mass ratio of 10:1; the degassing treatment is carried out under a vacuum of -0.08 MPa to -0.09 MPa; and the filtration is performed using a 200-mesh filter.